Head and neck (H&N) cancer is recognized as a significant threat to public health and a substantial economic challenge. The efficacy of radiotherapy widely used to treat H&N cancer is limited by severe adverse effects, such as mucositis. Currently, there are no drugs effectively preventing these complications. This situation constitutes a significant problem and an outstanding business opportunity for the development of new clinical radioprotectors to improve safety and efficiency of H&N cancer radiation therapy. This Phase I application is focused on exploring applicability of Protectan CBLB502 in minimizing radiation damage to healthy tissues in H&N cancer radiation treatment. The results of preliminary studies published by the investigators of this project provided the first evidence of feasibility of the proposed strategy. The Research Plan includes two specific aims that would (i) demonstrate protective effect of CBLB502 for healthy H&N tissues irradiated under close-to-clinical radiation regimen in mice; and (ii) explore the combination of radiation/CBLB502 treatment for improvement of efficacy and safety of radiotherapy in mouse model of H&N cancer. These milestones will provide a starting point for the Phase II program to complete preclinical studies, open an IND and start a clinical trial in patients with H&N cancers.